TRANSFUSION TRIGGER EXTENSION BY PLASMA EXPANDERS

通过血浆扩张器延长输血触发

• 批准号: 6527545
• 负责人: Marcos Intaglietta
• 金额: $ 36.69万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-01 至 2004-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6527545
• 关键词: blood /plasma substitute; blood transfusion; blood viscosity; blood volume; hamsters; hemodynamics; laboratory rat; microcirculation; nitric oxide; oxygen consumption; respiratory oxygenation; vascular resistance; vasoconstriction

DESCRIPTION (Adapted from the application): Colloidal or crystalloid solutions are used to restore blood volume up to the transfusion trigger of 7g Hb/dL. Their use beyond this threshold reduces oxygen carrying capacity, which limits tissue oxygen delivery and survival. This proposal examines the hypothesis that the lack of clinical benefit for plasma expanders (PEs) beyond the transfusion trigger is due to a microvascular malfunction, not due to a reduced oxygen carrying capacity. In particular, alteration of blood properties, including viscosity and oncotic pressure, beyond the transfusion trigger causes: 1) arteriolar vasoconstriction and decreased blood flow; 2) reduced functional capillary density (FCD); and, 3) lowered tissue oxygenation. A proposed mechanism underlying these changes is that below the transfusion trigger blood and plasma viscosity are reduced beyond the compensatory capacity of the cardiovascular system, which causes capillary pressure to decrease, capillaries to become obstructed, and a lowering of FCD. Furthermore, the viscosity of blood with conventional PEs is too low to generate endothelial NO through arteriolar wall shear stress, resulting in reduced vascular tone and increased mitochondrial O2 consumption. The proposed studies will use dextran and starch solutions with different viscosities as PEs in hamster studies using the skin fold microcirculatory model. The aim will be to partially restore the viscosity of the circulating blood to near normal values in extreme hemodilution (hemodilution beyond the transfusion trigger.) and examine the stated hypothesis by direct in vivo measurement of micro-p02 and micro-NO in blood and tissue, capillary pressure, blood flow velocity, functional capillary density and arteriolar reactivity. In particular the correlation between FCD, a key determinant of tissue survival, and NO regulation will be explored.

描述（根据申请改编）：胶体或晶体溶液 用于将血容量恢复至 7g Hb/dL 的输血触发点。 超过此阈值的使用会降低携氧能力，从而限制 组织氧输送和存活。该提案检验了以下假设： 除了输血之外，血浆增容剂 (PE) 缺乏临床益处 触发因素是微血管故障，而不是氧气减少 承载能力。特别是血液特性的改变，包括 粘度和胶体渗透压超出输血触发原因：1) 小动脉血管收缩和血流量减少； 2）功能减少 毛细血管密度（FCD）； 3) 组织氧合作用降低。提议的 这些变化背后的机制是低于输血触发血液 和血浆粘度降低超出了补偿能力 心血管系统，导致毛细血管压力降低，毛细血管 变得阻塞，并且 FCD 降低。此外，粘度 传统 PE 的血液浓度太低，无法通过 小动脉壁剪切应力，导致血管张力降低并增加 线粒体 O2 消耗。拟议的研究将使用葡聚糖和淀粉 使用皮肤进行仓鼠研究时使用不同粘度的溶液作为 PE 折叠微循环模型。目的是部分恢复粘度 在极端血液稀释中循环血液接近正常值 （血液稀释超出输血触发点。）并检查所述 通过直接体内测量血液中的微量 p02 和微量 NO 进行假设 组织、毛细血管压力、血流速度、功能毛细血管密度 和小动脉反应性。特别是 FCD 之间的相关性，一个关键 将探讨组织存活的决定因素和 NO 调节。